THE RABBIT SAPHENOUS-VEIN - A TISSUE-PREPARATION SPECIFICALLY ENRICHED IN NPY-Y1 RECEPTOR SUBTYPE

Neuropeptide Y (NPY), a co-transmitter in noradrenergic sympathetic nerves of the cardiovascular system, was tested on isolated segments of rabbit saphenous vein. NPY caused strong, long lastening and concentration dependent contraction resistant to adrenergic blockade. PYY, a NPY related peptide, shared this property. As pressor agents, both peptides were about 100-fold more potent than norepinephrine and at their highest concentrations caused a contraction of a similar magnitude as NE. Gradual shortening of N-terminal end of the NPY molecule caused major loss of potency and reduction of intrinsic activity; which suggests that the entire molecule is required to produce full biological activity in this vascular preparation. Addition of [Leu31,Pro34]pNPY, a NPY analog with specific agonist properties at Y1 receptors, mimicked the effect of NPY whereas NPY (13-36), a selective agonist at Y2 receptors, caused a 2 log unit shift to the right of the concentration response curve. These results suggest that the vasoconstrictor effect of NPY in rabbit saphenous vein results from a direct effect on smooth muscle cells and that the receptors involved are of the Y1 subtype.